Specific Antibodies in Oral Immunotherapy for Cow's Milk Allergy: Kinetics and Prediction of Clinical Outcome

Abstract

Background: Methods for predicting the clinical outcome of specific oral immunotherapy (OIT) would improve the safety of the therapy. Methods: We investigated 40 children aged 6-17 years with IgE-mediated cow's milk allergy (CMA) who either successfully completed OIT (n = 32) or discontinued the therapy due to adverse reactions (n = 8). From sera drawn before and after OIT, we analyzed specific IgA, IgG, IgG1 and IgG4 to cow's milk (CM), casein, β-lactoglobulin and ovalbumin (with enzyme-linked immunosorbent assay) and IgE to CM and hen's egg white [with enzymatic fluoroimmunoassay (Phadia ThermoFisher Scientific CAP system)]. As a reference, we also analyzed serum samples from 8- to 9-year-old children who either had no history of CMA (n = 76) or who had spontaneously recovered from IgE-mediated CMA (n = 56). Results: Levels of specific IgA, IgG, IgG1 and IgG4 to CM and casein, and CM-specific IgE prior to OIT were higher in children who discontinued the therapy than in those who achieved desensitization (p < 0.05). Adverse reactions in the entire population were associated with low IgG and IgG4, but high IgG1 levels to ovalbumin (p < 0.05). Specific IgA, IgG, IgG1 and IgG4 to CM proteins significantly increased and IgE to CM decreased during OIT in children who achieved desensitization (p < 0.01). In those who discontinued OIT, only IgG, IgG1 and IgG4 to CM increased significantly (p < 0.03) and CM IgE remained unchanged. Conclusions: High specific IgE, IgA and IgG-class antibodies to CM proteins appear to predict failure to achieve desensitization in CM OIT. Specific IgA and IgG-class antibodies to CM increase and CM IgE decreases during desensitization.

Oral and Sublingual Immunotherapy: Potential Causes for Eosinophilic Gastrointestinal Disorders?

“…Food-specific IgG4 decreases the following dietary elimination of the offending food [71] . Allergen-specific IgG and IgA increase after OIT [72] . Allergen-specific IgG subclasses (1-4) and IgA are able to bind to an allergen, act as an immune complex, and activate eosinophils; hence, they can induce eosinophil activation after SLIT or OIT and probably lead to the development of EoE [73] .…”

Food for thought

“…Baseline egg-specific IgE was reported to be a useful parameter to help identify children in whom egg OIT is more likely to be safe [46]. In the case of cow's milk allergy, high specific IgE, IgA, and IgG isotype antibodies to cow's milk were indicators of treatment failure in a study [47] of 40 children undergoing cow's milk OIT. These findings suggest novel strategies that may help with patient selection and risk stratification, which might maximize overall safety and effectiveness of immunotherapy.…”

Randomized Trial of Peanut Consumption in Infants at Risk for Peanut Allergy

“…Serum levels of peanut-specific IgE, IgG, and IgG4 antibodies were measured at each visit, since these are known biomarkers of allergic responses, antigen exposure, and potential immune modulation, respectively. 26,27 The peanut-specific IgG4:IgE ratio was calculated, since it has been reported that this ratio may additionally reflect immune modulation. 28 Immunoglobulin measurements were made with the use of the ImmunoCAP 100 and 250 assays (Thermo Fisher Scientific).…”